In the December 29, 2015 issue of the Journal, Taniguchi et al. (1) presented data from the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients with Severe Aortic Stenosis) registry, which constitutes the largest study to date on the natural history of asymptomatic severe aortic stenosis (AS), and included 1,517 patients treated conservatively and 291 treated with aortic valve replacement (AVR) (1). Their results are directly in line with a wide body of literature from smaller scale observational studies that have suggested a dismal prognosis for this disease. They showed that compared with patients who underwent AVR, conservatively managed patients had higher rates of hard clinical endpoints, even in the subgroup of patients without the traditional operative indications, such as left ventricular dysfunction or rapid disease progression. In addition, Taniguchi et al. showed that nearly one-half of conservatively managed patients underwent AVR at 5 years, and that surgical mortality was higher in patients who developed symptoms during that interval.

The investigators have to be commended for their large multicenter cohort and for the thorough analyses they performed, including a propensity-matched cohort and relevant sensitivity analyses, which all confirmed the results of the primary analysis. Lacking a randomized trial, these data are, by far, the best evidence available to encourage the expansion of the indication of AVR in asymptomatic patients with severe AS. However, 2 points should be clarified.

First, a significant proportion of the patients in the conservative group (62%) had an aortic valve area <1 cm2 without a mean gradient of >40 mm Hg or a maximal transaortic velocity >4 m/s compared with the AVR group (17%). Although not stated explicitly in the paper, it is assumed that appropriate advanced testing such as dobutamine echocardiography had been performed in these patients to rule out the possibility of a pseudo-stenosis. Even so, the enrollment of these patients is by itself problematic. Low-flow and/or low-gradient and paradoxical low-gradient AS bear pathophysiological processes, disease burdens, and prognostic implications distinct from normal flow and/or high-gradient (NF/HG) AS (2). By including patients with diverging disease states in the CURRENT AS registry, it is difficult to interpret the results and to generalize the findings to patients with true severe asymptomatic NF/HG AS. Therefore, the investigators are strongly encouraged to provide a sensitivity analysis that includes only patients with proven true severe NF/HG AS, as well as stating whether pseudo-stenosis was ruled out when appropriate.

Second, as outlined by the investigators, the asymptomatic state is increasingly difficult to assess in an aging patient population with low functional status. Patients without spontaneous symptoms, but who have limiting symptoms on exercise testing, have a different disease progression than patients without both spontaneous and exercise-induced symptoms (3). If a high proportion of the CURRENT AS registry is symptomatic on the treadmill, the study results are not as disruptive as they seem, because an indication to perform AVR in patients with abnormal exercise testing already exists. In that regard, if possible, an additional sensitivity analysis involving only patients for whom an exercise test proved negative would improve the scope of the study and allow generalizability of the findings to a truly asymptomatic patient population. A potential randomized trial of asymptomatic severe AS will need to perform a thorough patient selection process with exercise testing before enrollment.

Notwithstanding these 2 comments, the results provided by Taniguchi et al. further the debate of the optimal management of asymptomatic severe AS. In light of the 13.5% mortality rate while awaiting surgery (1), these patients deserve a randomized trial to finally settle the question. As the learning curve of transcatheter AVR (TAVR) improves, procedural mortality, major bleeding, and vascular complications rates consistently decrease according to data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry, which was presented in the same issue of the Journal(4). With recent studies justifying the expansion of the role of TAVR in lower risk populations (5), patients with asymptomatic severe AS should be the next population to be addressed in a TAVR trial. Because there is currently no formal indication for surgical AVR in these patients, this could be an exclusive niche for the less invasive TAVR procedure.

Footnotes

Please note: Dr. Marquis-Gravel has received a research grant from Bayer; and consulting fees from Bayer and AstraZeneca. Dr. Généreux has reported that he has no relationships relevant to the contents of this paper to disclose.

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